Acute Intermittent Porphyria: Causes, Symptoms & Treatment

Acute intermittent porphyria is the name given to a subtype of porphyria. In this inherited disorder, the body is unable to properly produce the blood pigment heme.

What is acute intermittent porphyria?

In this inherited disease, the organism is unable to correctly produce the blood pigment heme. Heme is a component of hemoglobin, the red blood pigment. Acute intermittent porphyria (AIP) is one of four acute forms of porphyria. The other three types are called hereditary coproporphyria, porphyria variegata and Doss porphyria. What they all have in common is sudden onset of abdominal pain, sometimes lasting for several days. Of particular medical relevance is acute intermittent porphyria, which is the most common form. It presents primarily in women.

Causes

Porphyrias such as acute intermittent porphyria are poorly understood because they occur very rarely. These related metabolic disorders are mostly noticeable in the nervous system and skin. As with the other porphyrias, the production of the protein-containing blood pigment heme is disturbed in acute intermittent porphyria. As a result of this process, precursors of heme, known as porphyrins, accumulate in the body and cause symptoms. Heme is a component of hemoglobin, the red blood pigment. The body needs special enzymes to produce heme. In the case of porphyria, however, there is a defect in at least one enzyme, which in turn has a negative effect on the production of heme. Acute intermittent porphyria is caused by a defect in the third enzyme in the heme synthesis pathway, which leads to a discontinuation of production. An autosomal dominant gene defect in porphobilinogen deaminase is responsible for porphyria. Autosomal dominant means independent of sex chromosomes. In acute intermittent porphyria, however, symptoms only occur in conjunction with infections, the influence of alcohol or the use of medications. Thus, these lead to the triggering of an acute disease flare. In most cases, acute intermittent porphyria presents between the ages of 20 and 40. The most common triggers of the disease are drugs such as sulfonamides, barbiturates or estrogen contained in the birth control pill, as well as alcohol, tobacco consumption, psychological stress and physical stress caused by infections or surgical procedures. Other reasons may include elevated iron levels, menstruation, and starvation due to fasting or dieting.

Symptoms, complaints, and signs

Acute intermittent porphyria presents with many different symptoms, making it difficult to make a diagnosis. However, in about 90 percent of all patients, there are no symptoms at all, while in other cases they become so severe that paralysis even occurs. The main symptoms of acute intermittent porphyria are acute abdominal pain. Neurological and psychiatric symptoms are also not uncommon. The symptoms appear in episodes that last one to two weeks. Sometimes, however, a longer period of symptoms is possible. In addition to severe colicky abdominal pain in the lower abdomen, affected individuals suffer from chronic constipation, vomiting, fever, and partial or complete paralysis. There are also sensory disturbances in smelling, hearing, seeing and tasting, as well as high blood pressure and palpitations. Another characteristic is reddish urine, which darkens as it progresses. Dark spots appear on the underwear. Likewise, psychological symptoms such as mood swings, confusion or delusions are conceivable.

Diagnosis and course

Diagnosing acute intermittent porphyria is sometimes difficult, even for experienced physicians. The typical porphyria symptoms are considered an important feature. The patient’s medical history can also be helpful if similar symptoms have already occurred in relatives. In order to make an exact diagnosis, the doctor takes urine, stool and blood samples. These are examined for porphyrins in a laboratory. An examination should be carried out if the patient is suffering from symptoms, because the values may drop during the course of the disease.If the urine is left to stand for a long time in acute intermittent porphyria, it takes on a red to dark red color in two-thirds of all patients. Another test that can be used is the reverse Ehrlich aldehyde assay, in which a drop of urine is added to one milliliter of Ehrlich reagent. In the case of acute intermittent porphyria, a cherry red discoloration occurs. In most cases, the course of AIP is favorable, provided appropriate therapy is given. However, complications such as respiratory distress, a lack of fluid, and damage to the liver and kidneys sometimes become apparent.

Complications

Acute intermittent porphyria is a rarely occurring disease that is more likely to affect women than men. The intermittent symptom swells latently in the body until a specific factor brings it to light. As a pathogenesis, a genetically determined enzyme defect is held responsible for the occurrence of porphyria. It does not appear in every affected person who has the predisposition to this symptom. The first episodes erupt as a young adult. The outbreaks are unpredictable and bring the patient significant as well as sometimes life-limiting complications. Triggering factors include external influences such as: stress, medications, alcohol, the menstrual cycle, infections, nicotine, and extreme diets. The symptom palette of outbreaks is variable and includes nausea as well as colic, circulatory problems, urine discoloration, neurological disorders, and psychological changes and hallucinations. If symptoms are misinterpreted or mishandled, further complications can occur and relapses can worsen. In some cases, there is a risk of life-threatening respiratory paralysis. Furthermore, affected individuals are prone to liver cancer and kidney damage as secondary complications. Due to the diversity of triggers and their accompanying symptoms, misdiagnoses can occur. Therefore, a thorough history is advised in the intensive care unit. The symptom is not curable. Strategies are developed to locate triggers, which the patient learns to avoid.

When should you see a doctor?

If acute gastrointestinal symptoms, cardiovascular symptoms, and sensory disturbances recur, the patient should see a doctor immediately if possible. The physician can determine whether the condition is acute intermittent porphyria based on the symptoms and some stool or urine samples. The diagnosis is facilitated by talking to the patient. If the symptoms have been present for more than one to two weeks, this indicates at least a serious illness that needs to be monitored. Increasing symptoms such as chronic constipation, vomiting, fever or paralysis, as well as problems with sight, smell, taste and hearing are clear warning signs of acute intermittent porphyria. If the disease is diagnosed on the basis of these symptoms, treatment must be given in any case. A visit to the doctor is recommended at the latest when there are physical symptoms of failure and a severe decrease in well-being. People who are regularly under stress, take medication, nicotine or alcohol, or are on an extreme diet should see a doctor immediately if the disease breaks out.

Treatment and therapy

Because acute intermittent porphyria is a genetic defect, there is no cure for the disease. For this reason, symptomatic treatment is given to relieve symptoms. In addition, the triggering factors should be avoided. If the AIP episodes are severe, intensive medical care in a hospital may be necessary. Thus, there is a risk of respiratory paralysis. If certain medications are responsible for the disease flare-up, their discontinuation is necessary. The patient receives additional heme arginine or glucose via an infusion. In this way, enriched heme precursors can be eliminated from the organism. Morphine derivatives and acetylsalicylic acid can be administered to treat the pain. An effective remedy for palpitations are reserpine and beta-blockers. In addition, the patient must refrain from alcohol. If triggering infections are present, it is important to treat them.

Prevention

Unfortunately, it is not possible to prevent acute intermittent porphyria because it is a genetic defect. However, there is an option to counteract the disease episodes by avoiding tobacco, alcohol, strong sunlight, and stress.

You can do it yourself

In this form of porphyria, the symptoms can be so severe that they stress patients not only physically but also psychologically. In addition, there are often neurological complaints as well. Both of these factors make accompanying psychotherapeutic treatment advisable. As with all forms of porphyria, all triggers that could trigger another episode should be avoided. Therefore, the patient with acute intermittent porphyria should not drink alcohol and avoid certain medications. The attending physician will determine which medications these are in detail after appropriate consultation. Patients with acute intermittent porphyria can also find a drug information sheet on the self-help website of EPP Germany (www.epp-deutschland.de). Nicotine must be taboo and a patient with acute intermittent porphyria should also avoid stressful situations as far as possible. Instead, he should pay attention to a regular daily rhythm, get enough sleep and exercise as much as possible. Relaxation exercises such as Reiki, yoga or Jacobson’s progressive muscle relaxation help to reduce daily stress. Extreme diets are also unnecessary stress. A balanced, healthy diet consisting of fresh foods such as fruits and vegetables and containing as little fat and sugar as possible is more advisable. This diet also strengthens the immune system, which is helpful in fighting infections. This is even more important considering that infections are among the triggers of acute intermittent porphyria.